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Fungal Secondary Metabolites in the “OMICS” Era

  • Susanne ZeilingerEmail author
  • Carlos García-Estrada
  • Juan-Francisco Martín
Chapter
Part of the Fungal Biology book series (FUNGBIO)

Abstract

Secondary metabolites produced by fungi have a tremendous impact on the human society; some are exploited for their antibiotic and pharmaceutical activities, others are involved in disease interactions with other organisms such as plants or animals.

The Springer book series on fungal biology includes two volumes on the Biosynthesis and Molecular Genetics of Fungal Secondary Metabolites accommodating the importance of these substances and the tremendous progress in the research on fungal secondary metabolism during recent years. While the first volume was published in 2014, you now have the second volume in your hand. In this introductory chapter, we bridge volume I—which covers the best-studied fungal secondary metabolites such as the penicillin and cephalosporin antibiotics, the immunosuppressive cyclosporine A, the anticholesterolemic agents lovastatin and compactin, the mycotoxins aflatoxin, ochratoxin A, roquefortine C, gibberellins, fusarins, fusaric acid and ergot alkaloids, the carotenoid, xanthophyll, bikaverin and fusarubin pigments, the pyripyropene meroterpenoids, and the iron-chelating siderophores—with other important aspects of secondary metabolites comprised in the second volume. Articles in the latter cover the spectrum from key transcriptional players in the regulation of secondary metabolite biosynthesis and its epigenetic control to approaches for the detection of new gene clusters and substances by genome mining, metagenomics/metatranscriptomics and metabolomics to the use of secondary metabolite profiles in fungal chemotaxonomy. Further reviews deal with the still underexplored fungal endophytes as a reservoir of novel biologically active natural products, the role of secondary metabolites in the interaction of fungi with plants and animals, and with a special group of fungal peptide secondary metabolites, the peptaibols.

Keywords

Fungal secondary metabolism Biosynthesis Gene cluster Genome Transcriptomics Metabolomics 

References

  1. 1.
    Hartmann T (2007) From waste products to ecochemicals: fifty years research of plant secondary metabolism. Phytochemistry 68(22–24):2831–2846PubMedCrossRefGoogle Scholar
  2. 2.
    Sachs J (1873) Lehrbuch der botanik. Leipzig: Wilhelm EngelmannGoogle Scholar
  3. 3.
    Martín JF, Gutiérrez S, Aparicio JF (2000) Secondary metabolites. In: Lederberg J (ed) Encyclopedia of microbiology. Academic, San Diego, pp 213–236Google Scholar
  4. 4.
    Keller NP, Turner G, Bennett JW (2005) Fungal secondary metabolism—from biochemistry to genomics. Nat Rev Microbiol 3(12):937–947PubMedCrossRefGoogle Scholar
  5. 5.
    Bennett JW (1983) Differentiation and secondary metabolism in mycelial fungi. In: Bennett JW (ed) Secondary metabolism and differentiation in fungi. Marcel Dekker, New York, pp 1–34Google Scholar
  6. 6.
    Turgeon BG, Bushley KE (2010) Secondary metabolism. In: Borkovich KE, Ebbole D (eds) Cellular and molecular biology of filamentous fungi. ASM, USA, p 376–395Google Scholar
  7. 7.
    Brakhage AA (2013) Regulation of fungal secondary metabolism. Nat Rev Microbiol 11(1):21–32PubMedCrossRefGoogle Scholar
  8. 8.
    Demain AL, Fang A (2000) The natural functions of secondary metabolites. Adv Biochem Eng Biotechnol 69:1–39PubMedGoogle Scholar
  9. 9.
    Gosio B (1893) Contributo all’etiologia della pellagra; ricerche chimiche e batteriologiche sulle alterazioni del mais. Giornale della Reale Accademia di Medicina di Torino 61:484–487Google Scholar
  10. 10.
    Abraham EP (1945) The effect of mycophenolic acid on the growth of Staphylococcus aureus in heart broth. Biochem J 39(5):398–408PubMedCentralPubMedGoogle Scholar
  11. 11.
    Florey HW, Jennings MA et al (1946) Mycophenolic acid; an antibiotic from Penicillium brevicompactum Dlerckx. Lancet 1(6385):46–49PubMedCrossRefGoogle Scholar
  12. 12.
    Anslow WK, Raistrick H (1931) Studies in the biochemistry of micro-organisms: 6-hydroxy-2-methylbenzoic acid, a product of the metabolism of glucose by Penicillium griseo-fulvum Dierckx. Biochem J 25(1):39–44PubMedCentralPubMedGoogle Scholar
  13. 13.
    Chain E, Florey HW, Gardner AD, Heatley NG, Jennings MA, Orr-Ewing J et al (1940) Penicillin as a chemotherapeutic agent. Lancet 236(6104):226–228CrossRefGoogle Scholar
  14. 14.
    Díez B, Gutiérrez S, Barredo JL, van Solingen P, van der Voort LHM, Martín JF (1990) The cluster of penicillin biosynthetic genes. J Biol Chem 265:16358–16365PubMedGoogle Scholar
  15. 15.
    Fierro F, Barredo JL, Díez B, Gutiérrez S, Fernández FJ, Martín JF (1995) The penicillin gene cluster is amplified in tandem repeats linked by conserved hexanucleotide sequences. Proc Natl Acad Sci U S A 92:6200PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Smith DJ, Burnham MK, Edwards J, Earl AJ, Turner G (1990) Cloning and heterologous expression of the penicillin biosynthetic gene cluster from Penicillum chrysogenum. Biotechnol (N Y) 8(1):39–41CrossRefGoogle Scholar
  17. 17.
    Gutierrez S, Velasco J, Fernandez FJ, Martin JF (1992) The cefG gene of cephalosporium acremonium is linked to the cefEF gene and encodes a deacetylcephalosporin C acetyltransferase closely related to homoserine O-acetyltransferase. J Bacteriol 174(9):3056–3064PubMedCentralPubMedGoogle Scholar
  18. 18.
    Martín JF, García-Estrada C, Zeilinger S (eds) (2014) Biosynthesis and molecular genetics of fungal secondary metabolites, vol I. Springer, New YorkGoogle Scholar
  19. 19.
    Finking R, Marahiel MA (2004) Biosynthesis of nonribosomal peptides1. Annu Rev Microbiol 58:453–488PubMedCrossRefGoogle Scholar
  20. 20.
    Garcia-Estrada C, Martin JF (2014) Penicillins. In: Martín JM, García-Estrada C, Zeilinger S (eds) Biosynthesis and molecular genetics of fungal secondary metabolites. Springer, New York, pp 17–42Google Scholar
  21. 21.
    Bloemendal S, Kück U (2014) Cephalosporins. In: Martín JM, García-Estrada C, Zeilinger S (eds) Biosynthesis and molecular genetics of fungal secondary metabolites. Springer, New York, pp 43–64Google Scholar
  22. 22.
    Velkov T, Lawen A (2014) Cyclosporines: biosynthesis and beyond. In: Martín JM, García-Estrada C, Zeilinger S (eds) Biosynthesis and molecular genetics of fungal secondary metabolites. Springer, New York, pp 65–88Google Scholar
  23. 23.
    Sørensen JL, Knudsen M, Hansen FT, Olesen C, Romans Fuertes P, Lee TV et al (2014) Fungal NRPS-dependent siderophores: from function to prediction. In: Martin JF, Garcia-Estrada C, Zeilinger S (eds) Biosynthesis and molecular genetics of fungal secondary metabolites. Springer, New York, pp 317–340Google Scholar
  24. 24.
    Kroken S, Glass NL, Taylor JW, Yoder OC, Turgeon BG (2003) Phylogenomic analysis of type I polyketide synthase genes in pathogenic and saprobic ascomycetes. Proc Natl Acad Sci U S A 100(26):15670–15675PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Linz JE, Wee JM, Roze LV (2014) Aflatoxin biosynthesis: regulation and subcellular localization. In: Martín JM, García-Estrada C, Zeilinger S (eds) Biosynthesis and molecular genetics of fungal secondary metabolites. Springer, New York, pp 89–110Google Scholar
  26. 26.
    Studt L, Tudzynski B (2014) Gibberellins and the red pigments bikaverin and fusarubin. In: Martín JM, García-Estrada C, Zeilinger S (eds) Biosynthesis and molecular genetics of fungal secondary metabolites. Springer, New York, pp 209–238Google Scholar
  27. 27.
    Dietrich D, Vederas JC (2014) Lovastatin, compactin, and related anticholesterolemic agents. In: Martín JM, García-Estrada C, Zeilinger S (eds) Biosynthesis and molecular genetics of fungal secondary metabolites. Springer, New York, pp 263–288Google Scholar
  28. 28.
    Fisch KM (2013) Biosynthesis of natural products by microbial iterative hybrid PKS-NRPS. RSC Adv 3(40):18228–18247. doi:10.1039/C3RA42661KCrossRefGoogle Scholar
  29. 29.
    Niehaus EM, Díaz-Sánchez V, von Bargen KW, Kleigrewe K, Humpf HU, Limón CM et al (2014) Fusarins and fusaric acid in fusaria. In: Martín JM, García-Estrada C, Zeilinger S (eds) Biosynthesis and molecular genetics of fungal secondary metabolites. Springer, New York, pp 239–262Google Scholar
  30. 30.
    Eley KL, Halo LM, Song Z, Powles H, Cox RJ, Bailey AM et al (2007) Biosynthesis of the 2-pyridone tenellin in the insect pathogenic fungus Beauveria bassiana. Chembiochem 8(3):289–297PubMedCrossRefGoogle Scholar
  31. 31.
    Bergmann S, Schumann J, Scherlach K, Lange C, Brakhage AA, Hertweck C (2007) Genomics-driven discovery of PKS-NRPS hybrid metabolites from Aspergillus nidulans. Nat chem biol 3(4):213–217PubMedCrossRefGoogle Scholar
  32. 32.
    Ávalos J, Díaz-Sánchez V, García-Martínez J, Castrillo M, Ruger-Herreros M, Limón CM (2014) Carotenoids. In: Martín JM, García-Estrada C, Zeilinger S (eds) Biosynthesis and molecular genetics of fungal secondary metabolites. Springer, New York, pp 149–186Google Scholar
  33. 33.
    Tudzynski P, Neubauer L (2014) Ergoit alkaloids. In: Martín JM, García-Estrada C, Zeilinger S (eds) Biosynthesis and molecular genetics of fungal secondary metabolites. Springer, New York, pp 303–316Google Scholar
  34. 34.
    Martín JF, Liras P, García-Estrada C (2014) Roquefortine C and related prenylated indole alkaloids. In: Martín JM, García-Estrada C, Zeilinger S (eds) Biosynthesis and molecular genetics of fungal secondary metabolites. Springer, New York, pp 111–128Google Scholar
  35. 35.
    Hoffmeister D, Keller NP (2007) Natural products of filamentous fungi: enzymes, genes, and their regulation. Nat Prod Rep 24(2):393–416PubMedCrossRefGoogle Scholar
  36. 36.
    Bok JW, Keller NP (2004) Laea, a regulator of secondary metabolism in Aspergillus spp. Eukaryot Cell 3(2):527–535PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Bayram O, Krappmann S, Ni M, Bok JW, Helmstaedt K, Valerius O et al (2008) Velb/vea/laea complex coordinates light signal with fungal development and secondary metabolism. Science 320(5882):1504–1506PubMedCrossRefGoogle Scholar
  38. 38.
    Kosalková K, García-Estrada C, Ullán RV, Godio RP, Feltrer R, Teijeira F et al (2009) The global regulator LaeA controls penicillin biosynthesis, pigmentation and sporulation, but not roquefortine C synthesis in Penicillium chrysogenum. Biochimie 91:214–225PubMedCrossRefGoogle Scholar
  39. 39.
    Palmer JM, Keller NP (2010) Secondary metabolism in fungi: does chromosomal location matter? Curr Opin Microbiol 13(4):431–436PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Reyes-Dominguez Y, Bok JW, Berger H, Shwab EK, Basheer A, Gallmetzer A et al (2010) Heterochromatic marks are associated with the repression of secondary metabolism clusters in Aspergillus nidulans. Mol Microbiol 76(6):1376–1386PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Andersen MR, Nielsen JB, Klitgaard A, Petersen LM, Zachariasen M, Hansen TJ et al (2013) Accurate prediction of secondary metabolite gene clusters in filamentous fungi. Proc Natl Acad Sci U S A 110(1):E99–E107PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Hertweck C (2009) Hidden biosynthetic treasures brought to light. Nat Chem Biol 5(7):450–452PubMedCrossRefGoogle Scholar
  43. 43.
    Brakhage AA, Schroeckh V (2011) Fungal secondary metabolites-strategies to activate silent gene clusters. Fungal Genet Biol 48(1):15–22PubMedCrossRefGoogle Scholar
  44. 44.
    Smedsgaard J, Nielsen J (2005) Metabolite profiling of fungi and yeast: from phenotype to metabolome by MS and informatics. J Exp Bot 56(410):273–286PubMedCrossRefGoogle Scholar
  45. 45.
    Fiehn O (2002) Metabolomics-the link between genotypes and phenotypes. Plant Mol Biol 48(1–2):155–171PubMedCrossRefGoogle Scholar
  46. 46.
    Krug D, Muller R (2014) Secondary metabolomics: the impact of mass spectrometry-based approaches on the discovery and characterization of microbial natural products. Nat Prod Rep 31(6):768–783PubMedCrossRefGoogle Scholar
  47. 47.
    Dhingra S, Lind AL, Lin HC, Tang Y, Rokas A, Calvo AM (2013) The fumagillin gene cluster, an example of hundreds of genes under vea control in Aspergillus fumigatus. Plos One 8(10):e77147PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Watrous J, Roach P, Alexandrov T, Heath BS, Yang JY, Kersten RD et al (2012 ) Mass spectral molecular networking of living microbial colonies. Proc Natl Acad Sci U S A 109(26):E1743–E1752PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Traxler MF, Watrous JD, Alexandrov T, Dorrestein PC, Kolter R (2013) Interspecies interactions stimulate diversification of the Streptomyces coelicolor secreted metabolome. mBio 4(4):pii: e00459-e004513. doi:10.1128/mBio.00459-13CrossRefGoogle Scholar
  50. 50.
    Liu WT, Kersten RD, Yang YL, Moore BS, Dorrestein PC (2011) Imaging mass spectrometry and genome mining via short sequence tagging identified the anti-infective agent arylomycin in Streptomyces roseosporus. J Am Chem Soc 133(45):18010–18013PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Moree WJ, Phelan VV, Wu CH, Bandeira N, Cornett DS, Duggan BM et al (2012) Interkingdom metabolic transformations captured by microbial imaging mass spectrometry. Proc Natl Acad Sci U S A 109(34):13811–13816PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Blackwell M (2011) The fungi: 1, 2, 3.. 5.1 million species? Am J Bot 98(3):426–438PubMedCrossRefGoogle Scholar
  53. 53.
    Kusari S, Hertweck C, Spiteller M (2012) Chemical ecology of endophytic fungi: origins of secondary metabolites. Chem Biol 19(7):792–798PubMedCrossRefGoogle Scholar
  54. 54.
    Stierle A, Strobel G, Stierle D (1993) Taxol and taxane production by Taxomyces andreanae, an endophytic fungus of Pacific yew. Science 260(5105):214–216PubMedCrossRefGoogle Scholar
  55. 55.
    Puri SC, Nazir A, Chawla R, Arora R, Riyaz-Ul-Hasan S, Amna T et al (2006) The endophytic fungus Trametes hirsuta as a novel alternative source of podophyllotoxin and related aryl tetralin lignans. J Biotechnol 122(4):494–510PubMedCrossRefGoogle Scholar
  56. 56.
    Kusari S, Lamshoft M, Zuhlke S, Spiteller M (2008) An endophytic fungus from Hypericum perforatum that produces hypericin. J Nat Prod 71(2):159–162PubMedCrossRefGoogle Scholar
  57. 57.
    Kusari S, Zuhlke S, Spiteller M (2009) An endophytic fungus from Camptotheca acuminata that produces camptothecin and analogues. J Nat Prod 72(1):2–7PubMedCrossRefGoogle Scholar
  58. 58.
    Schulz B, Boyle C, Draeger S, Römmert AK, Krohn K (2002) Endophytic fungi: a source of novel biologically active secondary metabolites. Mycol Res 106:996–1004CrossRefGoogle Scholar
  59. 59.
    Caballero Ortiz S, Trienens M, Rohlfs M (2013) Induced fungal resistance to insect grazing: reciprocal fitness consequences and fungal gene expression in the Drosophila-Aspergillus model system. Plos One 8(8):e74951PubMedCentralPubMedCrossRefGoogle Scholar
  60. 60.
    Doll K, Chatterjee S, Scheu S, Karlovsky P, Rohlfs M (2013) Fungal metabolic plasticity and sexual development mediate induced resistance to arthropod fungivory. Proc Biol Sci 280(1771):20131219PubMedCentralPubMedCrossRefGoogle Scholar
  61. 61.
    Chiang YM, Szewczyk E, Nayak T, Davidson AD, Sanchez JF, Lo HC et al (2008) Molecular genetic mining of the Aspergillus secondary metabolome: discovery of the emericellamide biosynthetic pathway. Chem Biol 15(6):527–532PubMedCentralPubMedCrossRefGoogle Scholar
  62. 62.
    Lo HC, Entwistle R, Guo CJ, Ahuja M, Szewczyk E, Hung JH et al (2012) Two separate gene clusters encode the biosynthetic pathway for the meroterpenoids austinol and dehydroaustinol in Aspergillus nidulans. J Am Chem Soc 134(10):4709–4720PubMedCentralPubMedCrossRefGoogle Scholar
  63. 63.
    Jansen C, von Wettstein D, Schafer W, Kogel KH, Felk A, Maier FJ (2005) Infection patterns in barley and wheat spikes inoculated with wild-type and trichodiene synthase gene disrupted Fusarium graminearum. Proc Natl Acad Sci U S A 102(46):16892–16897PubMedCentralPubMedCrossRefGoogle Scholar
  64. 64.
    Collemare J, Billard A, Bohnert HU, Lebrun MH (2008) Biosynthesis of secondary metabolites in the rice blast fungus Magnaporthe grisea: the role of hybrid pks-nrps in pathogenicity. Mycol Res 112(Pt 2):207–215PubMedCrossRefGoogle Scholar
  65. 65.
    Banik JJ, Brady SF (2010) Recent application of metagenomic approaches toward the discovery of antimicrobials and other bioactive small molecules. Curr Opin Microbiol 13(5):603–609PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Susanne Zeilinger
    • 1
    • 2
    Email author
  • Carlos García-Estrada
    • 3
  • Juan-Francisco Martín
    • 4
  1. 1.Institute of Chemical EngineeringVienna University of TechnologyWienAustria
  2. 2.Institute of MicrobiologyUniversity of InnsbruckInnsbruckAustria
  3. 3.INBIOTEC (Instituto de Biotecnología de León)LeónSpain
  4. 4.Department of Molecular Biology, Microbiology SectionUniversity of LeónLeónSpain

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